The purpose of this research program is to analyze the effects of the halogenated amphetamines, 4-chloroamphetamine (PCA) and fenfluramine (FFA), on the mammalian central nervous system. Recent studies have suggested that these compounds have significant neurotoxicity upon a restricted group of midbrain serotonin neurons. A preliminary replication of this work confirms the original observations but indicates that the neurotoxicity is more widespread than first reported and may involve non-serotonin neurons. The proposed research will include the following. 1) A detailed histological study of the effects of high dose (100 umole/kg) PCA and FFA on the rat central nervous system at 1,3,4,5,6,10 and 30 days after administration using light microscopy. 2) A detailed histological study of chronic low dose (12.5 umole/kg) PCA and FFA on the rat central nervous system. 3) An ultrastructural study of acute high dose and chronic low dose FFA on neurons of the tegmental reticular nucleus of the rat. 4) An histological study of the effects of PCA and FFA administered to pregnent rats during the last 10 days of gestation on the central nervous system of their pups in the early neonatal period and after puberty. 5) A detailed histological study of chronic low dose FFA administration on the central nervous system of the macaque monkey. The objective of the program is to determine if this class of drugs which has come into wide clinical usage has sufficient permanent neurotoxicity to represent a danger to the human nervous system.